Recent medicinal chemistry of the histamine H3 receptor.

Publisher Summary Following the cloning of the histamine H3 receptor cDNA, the level of activity amongst both academic and pharmaceutical company laboratories has increased enormously. This activity has provided a greater understanding of the basic biology of the target, answering many questions about the potential therapeutic roles for histamine H3 receptor ligands and also raising some more fundamental questions about the nature of the receptor system. At the same time, the medicinal chemistry of the various ligands has also changed, primarily owing to the involvement of several pharmaceutical companies who have exploited high-throughput screening techniques to find novel templates for drug design. One consequence of these efforts is the discovery of numerous non-imidazole H3 antagonists, capable of addressing the shortcomings of the earlier imidazole-based compounds. Several of the newer structures appear to have acceptable drug-like properties with several advancing into the clinic and thus, the role of these agents as therapeutics should soon be established.